Signaling muts undergo dynamic losses and gains from diagnosis through REL. (A) Bar plot depicting the relative proportions of different mut trajectories between diagnosis and REL1 in individual patients (n = 76), filtered for genes with at least 4 variants identified across the cohort. Colors indicate whether the mut was stable (gray), lost (yellow), or gained (teal) from diagnosis through REL. The number to the right indicates the total number of variants identified among paired diagnosis and REL samples for the indicated gene; within each section of the bar plot, the numbers indicate the number of variants within each category. (B) Violin plot depicting the difference in VAFs (ΔVAF) between REL and diagnosis. Negative values indicate a lower VAF at REL, whereas positive values indicate a higher VAF. (C-E) Scatterplot indicating VAF at diagnosis (x-axis) and REL1 (y-axis) for (C) IDH1 and IDH2; (D) DNMT3A, TET2, and ASXL1; and (E) FLT3, NPM1, and NRAS. Each point represents 1 variant in a specific patient, matched across time. (F-I) Contingency tables evaluating the association between FLT3i treatment (F), STAG2 muts at diagnosis (G), PTPN11 muts at diagnosis (H), or NRAS muts at diagnosis (I) with FLT3 mut loss in panels F-G, FLT3 mut gain in panel H, or WT1 mut loss in panel I. In the event that a patient had multiple variants in the same gene, the variant with the largest change in VAF between diagnosis and REL was retained. Statistics were determined by Firth penalized logistic regression models; for panels G-H, FLT3i treatment status was included as a covariate in the model. OR, odds ratio.